title: Safety, adherence and acceptability of intermittent tenofovir/emtricitabine as HIV pre-exposure prophylaxis (PrEP) among HIV-uninfected Ugandan volunteers living in HIV-serodiscordant relationships: a randomized, clinical trial.
abstract: BACKGROUND
  Efficacy of oral pre-exposure prophylaxis (PrEP) in prevention of HIV acquisition has been evaluated using a daily regimen. However, adherence to long term daily medication is rarely perfect. Intermittent regimen may be a feasible alternative. Preclinical studies have demonstrated effectiveness of intermittent PrEP in SHIV prevention among animals. However, little is known about intermittent PrEP regimens.
  
  
  METHODS
  Seventy two HIV-uninfected volunteers in HIV serodiscordant couple relationships in Uganda were randomly assigned to receive daily oral Tenofovir/Emtricitabine (TDF/FTC-Truvada) or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral TDF/FTC or placebo in a 2:1:2:1 ratio. Volunteers and study staff were blinded to drug assignment, but not to regimen assignment.
  
  
  METHODS
  Volunteers were followed for 4 months after randomization, with monthly clinical and laboratory safety assessments and comprehensive HIV risk reduction services. Adherence was monitored using medication event monitoring system (MEMS) and self-report. Sexual activity data were collected via daily short text message (SMS) and self-report. HIV-specific immune responses were assessed by IFN-γ ELISPOT.
  
  
  RESULTS
  Both daily and intermittent oral TDF/FTC regimens were well tolerated. Median MEMS adherence rates were 98% (IQR: 93-100) for daily PrEP regimen, 91% (IQR: 73-97) for fixed intermittent dosing and 45% (IQR: 20-63) for post-coital dosing. SMS response rate was 74%, but increased to 80% after excluding server outages; results may have been affected by the novelty of this measure. The majority of volunteers expressed willingness with no particular preference for either regimen.
  
  
  CONCLUSIONS
  Both daily and intermittent oral PrEP dosing regimens were safe. Adherence was high for daily and fixed intermittent dosing; post-coital dosing was associated with poor adherence. Fixed intermittent PrEP regimens may be feasible especially if a minimum effective drug concentration correlating with HIV prevention can be achieved with this dosing.
  
  
  BACKGROUND
  Clinicaltrials.gov number NCT00931346.
authors.affiliation: Medical Research Council (MRC)/Uganda Virus Research Institute (UVRI) Uganda Research Unit on AIDS, Entebbe, Uganda.
authors.forename: Freddie M
authors.initials: FM
authors.lastname: Kibengo
authors.forename: Eugene
authors.initials: E
authors.lastname: Ruzagira
authors.forename: David
authors.initials: D
authors.lastname: Katende
authors.forename: Agnes N
authors.initials: AN
authors.lastname: Bwanika
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Bahemuka
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Haberer
authors.forename: David R
authors.initials: DR
authors.lastname: Bangsberg
authors.forename: Burc
authors.initials: B
authors.lastname: Barin
authors.forename: James F
authors.initials: JF
authors.lastname: Rooney
authors.forename: David
authors.initials: D
authors.lastname: Mark
authors.forename: Paramesh
authors.initials: P
authors.lastname: Chetty
authors.forename: Patricia
authors.initials: P
authors.lastname: Fast
authors.forename: Anatoli
authors.initials: A
authors.lastname: Kamali
authors.forename: Frances H
authors.initials: FH
authors.lastname: Priddy
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission; D006801:Humans; D008297:Male; D063065:Organophosphonates / Q000008:administration & dosage*; D010349:Patient Compliance; D000068698:Tenofovir; D014454:Uganda
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine